Work

Expression of αvβ8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice

Year: 2010

Type: article

Abstract: Th17 cells promote a variety of autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. TGF-β is required for conversion of naive T cells to Th17 cells, but the mechanisms regulating this process are unknown. Integrin αvβ8 on DCs can activate TGF-β, and this process contributes to the development of induced Tregs. Here, we have now shown that integrin αvβ8 expression on DCs plays a critical role in the differentiation of Th17 cells. Th17 cells were nearly absent in the colons of mice lacking αvβ8 expression on DCs. In addition, these mice and the DCs harvested from them had an impaired ability to convert naive T cells into Th17 cells in vivo and in vitro, respectively. Importantly, mice lacking αvβ8 on DCs showed near-complete protection from experimental autoimmune encephalomyelitis. Our results therefore suggest that the integrin αvβ8 pathway is biologically important and that αvβ8 expression on DCs could be a therapeutic target for the treatment of Th17-driven autoimmune disease.

Source: Journal of Clinical Investigation

DOI: 10.1172/jci43786

Authors: Andrew C. Melton, Samantha L. Bailey-Bucktrout, Mark A. Travis, Brian T. Fife, Jeffrey A. Bluestone, Dean Sheppard

Institutions: University of California, San Francisco, Wellcome Centre for Cell-Matrix Research, University of Manchester, University of Minnesota

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, Biotechnology and Biological Sciences Research Council, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases